Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye.

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

Clinical efficacy and safety of Chinese herbal injections in combination with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis of 140 randomized controlled trials.

Background and aim: Chinese herbal injection (CHI) is a widely used preparation for advanced non-small cell lung cancer (NSCLC) treatment to alleviate the adverse drug reactions and enhance the clinical efficacy of chemotherapy. However, its efficacy and safety in combination with platinum-based chemotherapy (PBC) remain poorly understood owing to the lack of high-level evidence in the face of a wide variety of CHIs. Therefore, in this study, we aimed to explore the efficacy and safety of CHIs in combination with PBC regimens in the treatment of mid- and advanced NSCLC. Methods: Systematic evaluation and meta-analysis were conducted as per the Preferred Reporting Project for Systematic Evaluation and Meta-Analysis Protocols (PRISMA-P). Seven databases were comprehensively searched for relevant randomized controlled trials (RCTs) through August 1, 2022. The quality of each study was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed using Revman 5.3, with dichotomies expressed as risk ratio (RR) and 95% confidence interval (CI). Objective response rate (ORR) and disease control rate (DCR) were selected as the primary outcomes, with quality of life (QoL) and toxic side effects as secondary outcomes. Results: A total of 140 RCTs were included in this study. The results of the meta-analysis suggested that, compared with PBC alone, PBC combined with CHIs significantly improved the ORR (RR=1.35, 95% CI: 1.30-1.41, P<0.001), DCR (RR=1.15, 95% CI: 1.13-1.18, P<0.001) and QoL (RR=1.29, 95% CI: 1.24-1.33, P<0.001). Moreover, the combination treatment reduced chemotherapy-induced leukopenia (RR=0.69, 95% CI: 0.64-0.75, P<0.001), anemia (RR=0.70, 95% CI: 0.62-0.79, P<0.001), thrombocytopenia (RR=0.68, 95% CI: 0.62-0.75, P<0.001), nausea and vomiting (RR=0.69, 95% CI: 0.63-0.76, P<0.001), diarrhea (RR=0.59, 95% CI: 0.48-0.73, P<0.001), and constipation (RR=0.68, 95% CI: 0.54-0.86, P=0.001). Conclusion: According to the available evidence, CHIs in combination with PBC can improve clinical efficacy and reduce the toxic side effects in the treatment of advanced NSCLC. However, considering the study's limitations, more rigorous and high-quality studies are needed to further confirm the results. Systematic review registration: https://inplasy.com/inplasy-2022-1-0104/, identifier INPLASY202210104.

Signaling pathways regulated by natural active ingredients in the fight against exercise fatigue-a review.

Exercise fatigue is a normal protective mechanism of the body. However, long-term fatigue hinders normal metabolism and exercise capacity. The generation and recovery from exercise fatigue involves alterations in multiple signaling pathways, mainly AMPK, PI3K/Akt, Nrf2/ARE, NF-κB, PINK1/Parkin, and BDNF/TrkB, as well as MAPK signaling pathways that mediate energy supply, reduction of metabolites, oxidative stress homeostasis, muscle fiber type switching, and central protective effects. In recent studies, a rich variety of natural active ingredients have been identified in traditional Chinese medicines and plant extracts with anti-fatigue effects, opening up the field of research in new anti-fatigue drugs. In this review we give an overview of the signaling pathways associated with the activity of natural food active ingredients against exercise fatigue. Such a comprehensive review is necessary to understand the potential of these materials as preventive measures and treatments of exercise fatigue. We expect the findings highlighted and discussed here will help guide the development of new health products and provide a theoretical and scientific basis for future research on exercise fatigue.

Combining transcriptomic analysis and network pharmacology to explore the mechanism by which Shaofu Zhuyu decoction improves diabetes mellitus erectile dysfunction.

BACKGROUND: Erectile dysfunction is common among the complications of diabetes mellitus. Shaofu Zhuyu decoction (SFZYD) is commonly used to treat diabetic mellitus erectile dysfunction (DMED). However, its main active components and specific mechanism are still unknown. PURPOSE: To confirm the activity of SFZYD in improving DMED, explore the main active components of SFZYD, and clarify the underlying mechanism. METHODS: A diabetic rat model was induced with streptozotocin (STZ). After intragastric administration, erectile function was assessed by the maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP). Corpus cavernosum fibrosis was evaluated by Masson staining, and ELISA methods were used to determine the serum levels of IL-6, TNF-α, IL-10, IL-4 and IL-1ß to evaluate inflammation. Then, the main active components of SFZYD were identified by UPLC‒MS/MS. Finally, the target and biological mechanism of SFZYD in improving DMED were predicted by combined network pharmacology and transcriptomics, which was also validated by molecular docking and cellular thermal shift assay (CETSA) experiments. RESULTS: SFZYD significantly improved erectile dysfunction and inhibited inflammatory responses and local tissue fibrosis in diabetic rats. A total of 1846 active components were identified by UPLC‒MS/MS, and isorhamnetin was the main active component. The transcriptomic results were used to identify differentially expressed genes among the control, DM and SFZYD groups, and 1264 differentially expressed genes were obtained from the intersection. The network pharmacology results showed that SFZYD acts on core targets such as AKT1, ALB, HSP90AA1 and ESR1 through core components such as isorhamnetin, quercetin and chrysophanic acid. Further combined analysis revealed that multiple targets, such as CYP1B1, DPP4, NOS2 and LCN2, as well as the regulation of the PI3K-AKT signaling pathway, may be important mechanisms by which SFZYD improves DMED. Molecular docking verification showed that isorhamnetin, the key component of SFZYD, has good binding ability with several core targets, and its binding ability with CYP1B1 was the strongest. The CETSA results showed that isorhamnetin binds to CYP1B1 in CCECs. CONCLUSION: SFZYD improves DMED, inhibits the inflammatory response and alleviates local tissue fibrosis. The combined application of transcriptomic, network pharmacology, molecular docking and CETSA approaches was helpful for revealing the mechanism by which SFZYD improves DMED, which may be related to the regulation of CYP1B1 and the PI3K-Akt signaling pathway.

Novel iron-chelating peptide from egg yolk: Preparation, characterization, and iron transportation.

In this work, an egg yolk protein hydrolysate (EYPH) with a high iron-chelating ability (87.32%) was prepared. The fractionation using 60% (v/v) ethanol concentration (E3 fraction) led to the efficiently accumulating the iron-chelating peptides in EYPH. The characterization results showed that iron mainly chelated with carboxyl, amino and phosphate groups of peptides. From E3 fraction, six iron-chelating peptides with MW ranging from 1372.36 to 2937.04 Da were identified and a hypothesized molecular model of DDSSSpSpSpSpSpSVLSK-Fe was simulated. In vitro stability determination showed that E3-Fe chelate owned a good heat, alkalinity and digestion tolerance, but a relatively bad acid tolerance. Finally, iron transport analysis showed that iron in the E3-Fe would be absorbed in caco-2 cell membrane more effectively than that of iron salts, indicating that it was possible to apply the E3-Fe complex as iron supplements.

Tyrosinase-activated Nanocomposites for Double-Modals Imaging Guided Photodynamic and Photothermal Synergistic Therapy.

Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr-obes-based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic-photothermal activity by regulating the balance between radiative decay and non-radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria-targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR-activated imaging and photodynamic-photothermal therapy of melanoma. The development of TYR-activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.

The role and regulation mechanism of Chinese traditional fitness exercises on the bone and cartilage tissue in patients with osteoporosis: A narrative review.

Osteoporosis (ops) is a systemic degenerative bone disease characterized by bone mass reduction, bone mineral density loss, bone microstructure destruction, bone fragility, and increased fracture susceptibility. Thus far, drug therapy is the main method used to prevent and treat osteoporosis. However, long-term drug treatment will inevitably lead to drug resistance and certain side effects. In response, rehabilitation treatment is generally recommended, which involves drug supplementation combined with the treatment. A Chinese traditional fitness exercise is an organic combination of sports and traditional Chinese medicine with a series of advantages such as being safe, convenient, non-toxic, and harmless. Hence, it is one of the rehabilitation methods widely used in clinical practice. By searching the CNKI, PubMed, Web of Science, Embase, Cochrane Library, and other relevant databases, our research clarifies the current situation of four kinds of Chinese traditional fitness exercises widely used in clinical practice, namely, Taijiquan, Baduanjin, Wuqinxi, and Yijin Jing. In addition, the molecular mechanism of osteoporosis is summarized in this study. Based on the research, Chinese traditional fitness exercises are expected to directly stimulate the bone through a mechanical load to improve bone density. Moderate and regular traditional Chinese fitness exercises also improve osteoporosis by regulating the endocrine system with the secretion of hormones and factors such as estrogen and irisin, which are beneficial for bone formation. Finally, the purpose of promoting bone formation, reducing bone loss, and preventing and treating osteoporosis is achieved. The various means of Chinese traditional fitness exercises have different emphases, and the effect of improving bone density differs in various parts of the body. The exercisers may choose the exercise flexibly based on their own needs. Chinese traditional fitness exercises can improve the bone density of the exercisers and relieve pain, improve balance, and regulate the psychological state. Consequently, it is worth promoting to be applied in clinical practices.

Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.

Inverse Association Between Baseline Plasma Selenium Concentrations and Risks of Renal Function Decline in Hypertensive Adults.

BACKGROUND: The kidney has the highest level of selenium (Se) in the body, but the role of plasma Se in chronic kidney disease is uncertain. OBJECTIVE: We aimed to investigate the longitudinal association between baseline plasma Se and renal function decline in adults with hypertension and to explore possible effect modifiers. METHODS: This was a post hoc analysis of 935 men and women with hypertension aged 40 to 75 years from a folic-acid intervention trial (the China Stroke Primary Prevention Trial) in China. The baseline plasma Se was analyzed both as a continuous variable and as tertiles. The primary outcome was a rapid decline in renal function, defined as a mean decline in the estimated glomerular filtration rate of ≥ 5 mL/(min × 1.73 m2) per year. RESULTS: The median follow-up duration from baseline to outcome was 4.4 years. After multivariate adjustment, there was an inverse association between plasma Se and a rapid decline in renal function (per 10-unit increment; OR: 0.85; 95% CI: 0.73, 0.99). When the baseline plasma Se was assessed as tertiles, compared to the lowest tertile (<74.5 µg/L), a lower trend of the primary outcome was found in the second tertile (74.5 to < 89.4 µg/L; OR: 0.60; 95% CI: 0.34, 1.07) and the highest tertile (89.4 to <150 µg/L; OR: 0.42; 95% CI: 0.22, 0.80; Ptrend = 0.006). Furthermore, the Se-renal association was more pronounced among participants with folic acid treatment or with a higher baseline folate concentration (both Pinteraction values < 0.05). CONCLUSIONS: In this sample of Chinese adults with hypertension, baseline plasma Se concentrations were inversely associated with the risk of renal function decline. The China Stroke Primary Prevention Trial was registered at clinicaltrials.gov as NCT00794885.

[Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy].

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

[Optimization of processing technology of braised Rehmanniae Radix based on multiple indexes and response surface technology and correlation between components and color].

This study aims to explore the key factors influencing the processing of braised Rehmanniae Radix, optimize the processing, and determine the correlation between the components in different processed products and chroma values, which is expected to add quantitative indexes for the processing of braised Rehmanniae Radix and better control the processing. The weights of the indexes catalpol, rehmannioside D, verbascoside, isoacteoside, 5-hydroxymethylfurfural, reducing sugar, and appearance were calculated based on analytic hierarchy process(AHP) in combination with coefficient of variation, and the overall desirability(OD) was obtained. Box-Behnken design was used to explore the optimal amount of water added, time for soaking with rice wine, and steaming time in the processing of braised Rehmanniae Radix. Colorimeter was employed to determine the chroma of 17 samples and raw samples, and SPSS, Prism, and other software to investigate the correlation between the components in braised Rehmanniae Radix and the chroma values. The results showed that each factor influenced the processing, and the influence followed the order of steaming time>amount of water added>time for soaking with rice wine. The optimal processing process is as below: A total of 100 g medicinal material was added with 7 times of water, followed by soaking with rice wine for 5 h and steaming in a pot for 6 h. The correlation analysis suggested the extremely significantly positive correlation between L~* and content of catalpol, between a~* and 5-hydroxymethylfurfural content, and between b~* and catalpol content, and the extremely significantly negative correlation between L~* and the content of 5-hydroxymethylfurfural and reducing sugar, and between b~* and the content of 5-hydroxymethylfural and reducing sugar. In this experiment, response surface methodology was used to optimize the processing technology of braised Rehmanniae Radix and the optimized process was rational and feasible. The content of chemical components in braised Rehmanniae Radix was significantly correlated with the chroma. This study provided a new method for the quality evaluation of braised Rehmanniae Radix.

Effects of selenium yeast and jujube powder dietary supplements on conformational and functional properties of post-mortem chicken myofibrillar protein.

The aim of the study was to evaluate the effects of selenium yeast and jujube powder on the structure and functional properties of post-mortem myofibrillar protein (MP) in white feather broilers. Changes in the structure (surface hydrophobicity, secondary structure, and tertiary structure), functional properties (solubility, turbidity, emulsifying, and foaming characteristics), and gel properties (gel strength, springiness, and water-holding capacity) of the MPs of white feather broiler, which were fed with different concentrations of selenium yeast or/and jujube powder (selenium yeast: 0,0.3, and 0.6 mg/kg; jujube powder: 8% to replace corn) for 42 days, were determined at 0, 24, and 72 h post-mortem. The results showed that with increasing concentrations of selenium yeast and jujube powder in the diet, the α-helix content, solubility, emulsification, and foaming of post-mortem chicken MP increased significantly (P < 0.05). The gel strength, springiness, and water-holding capacity of MP also increased, but the differences between the treatment groups were not significant (P > 0.05). In addition, the ß-folding content and turbidity of MP decreased significantly (P < 0.05). Both the increase in selenium yeast levels and the addition of jujube powder improved the structural integrity and functional properties of MP. The best improvement effect was found in the combination group of high-dose selenium yeast and jujube powder, and there were significant interactions between them in the indices of α-helix, ß-folding, turbidity, emulsification, and foam stability of MP. In conclusion, supplementing diets with seleniumyeast and jujube powder could maintain the structural stability of MPs in post-mortem chicken breast, leading to good functional properties. The results of this study may provide new insights into the effects of pre-slaughter feeding on post-mortem muscle MP conformation control and quality improvement.

Medicinal plants and their secondary metabolites in alleviating knee osteoarthritis: A systematic review.

BACKGROUND: With the increasing ages of the general population, the incidence of knee osteoarthritis (KOA) is also rising, and KOA has become a major health problem worldwide. Recently, medicinal plants and their secondary metabolites have gained interest due to their activity in treating KOA. In this paper, a comprehensive systematic review of the literature was performed concerning the effects of medicinal plant extracts and natural compounds against KOA in recent years. The related molecular pathways of natural compounds against KOA were summarized, and the possible crosstalk among components in chondrocytes was discussed to propose possible solutions for the current situation of treating KOA. PURPOSE: This review focused on the molecular mechanisms by which medicinal plants and their secondary metabolites act against KOA. METHODS: Literature searches were performed in the PUBMED, Embase, Science Direct, and Web of Science databases for a 10-year period from 2011 to 2022 with the search terms "medicinal plants," "bioactive compounds," "natural products," "phytochemical," "knee osteoarthritis," "knee joint osteoarthritis," "knee osteoarthritis," "osteoarthritis of the knee," and "osteoarthritis of knee joint." RESULTS: According to the results, substantial plant extracts and secondary metabolites show a positive effect in fighting KOA. Plant extracts and their secondary metabolites can affect the diagnostic and prognostic biomarkers of KOA. Natural products inhibit the expression of MMP1, MMP3, MMP19, syndecan IV, ADAMTS-4, ADAMTS-5, iNOS, COX-2, collagenases, IL-6, IL-1ß, and TNF-α in vitro and in vivo and . Cytokines also upregulate the expression of collagen II and aggrecan. The main signaling pathways affected by the extracts and isolated compounds include AMPK, SIRT, NLRP3, MAPKs, PI3K/AKT, mTOR, NF-κB, WNT/ß-catenin, JAK/STAT3, and NRF2, as well as the cell death modes apoptosis, autophagy, pyroptosis, and ferroptosis. CONCLUSION: The role of secondary metabolites in different signaling pathways supplies a better understanding of their potential to develop further curative options for KOA.

Network Meta-Analysis of Acupoint Catgut Embedding in Treatment of Simple Obesity.

Objective: To evaluate the clinical efficacy of acupoint catgut embedding in the treatment of simple obesity through network meta-analysis. Methods: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP database (VIP) were searched by using computer from 2011 to August 2021, and 35 RCT studies were retrieved. The quality of the literature was evaluated using the modified Jadad scoring table, and Stata 15.0 software was used for traditional meta-analysis and network meta-analysis. Results: Thirty-five RCTs (3040 cases in total) were included. Acupoint embedding, acupuncture, electroacupuncture, TCM, acupoint embedding + acupuncture, acupoint embedding + exercise diet therapy, acupoint embedding + TCM, exercise diet therapy, acupoint embedding + moxibustion, and acupoint embedding + cupping were investigated in the studies. The results of network meta-analysis were as follows: in terms of total effective rate, acupoint catgut embedding was superior to acupuncture, electroacupuncture, and exercise diet therapy (P < 0.05); electroacupuncture, acupoint catgut embedding + acupuncture, acupoint catgut embedding + exercise diet therapy, acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to acupuncture (P < 0.05); acupoint catgut + moxibustion was superior to electroacupuncture (P < 0.05); acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to TCM treatment (P < 0.05); and electroacupuncture, acupoint catgut, acupoint catgut + acupuncture, acupoint catgut + exercise diet therapy, acupoint catgut + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to sports diet therapy (P < 0.05). Regarding weight loss, acupuncture treatment was superior to acupoint catgut embedding therapy (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to acupuncture and electroacupuncture treatment (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, and acupoint catgut embedding + moxibustion were superior to TCM treatment (P < 0.05); and acupoint catgut embedding, acupoint catgut embedding + acupuncture, catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to exercise diet therapy (P < 0.05). In terms of BMI reduction, acupoint catgut embedding + moxibustion and acupoint catgut embedding + cupping were more evident than acupuncture treatment (P < 0.05); and acupoint catgut embedding + moxibustion was more evident than electroacupuncture treatment (P < 0.05). Conclusion: Acupoint catgut embedding and its combination with other therapies are the first choice for the treatment of simple obesity.

Luteolin Ameliorates Methamphetamine-Induced Podocyte Pathology by Inhibiting Tau Phosphorylation in Mice.

Methamphetamine (METH) can cause kidney dysfunction. Luteolin is a flavonoid compound that can alleviate kidney dysfunction. We aimed to observe the renal-protective effect of luteolin on METH-induced nephropathies and to clarify the potential mechanism of action. The mice were treated with METH (1.0-20.0 mg/kg/d bodyweight) for 14 consecutive days. Morphological studies, renal function, and podocyte specific proteins were analyzed in the chronic METH model in vivo. Cultured podocytes were used to support the protective effects of luteolin on METH-induced podocyte injury. We observed increased levels of p-Tau and p-GSK3ß and elevated glomerular pathology, renal dysfunction, renal fibrosis, foot process effacement, macrophage infiltration, and podocyte specific protein loss. Inhibition of GSK3ß activation protected METH-induced kidney injury. Furthermore, luteolin could obliterate glomerular pathologies, inhibit podocyte protein loss, and stop p-Tau level increase. Luteolin could also abolish the METH-induced podocyte injury by inactivating GSK3ß-p-Tau in cultured podocytes. These results indicate that luteolin might ameliorate methamphetamine-induced podocyte pathology through GSK3ß-p-Tau axis.

Icariside II Attenuates Methamphetamine-Induced Neurotoxicity and Behavioral Impairments via Activating the Keap1-Nrf2 Pathway.

Chronic and long-term methamphetamine (METH) abuse is bound to cause damages to multiple organs and systems, especially the central nervous system (CNS). Icariside II (ICS), a type of flavonoid and one of the main active ingredients of the traditional Chinese medicine Epimedium, exhibits a variety of biological and pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. However, whether ICS could protect against METH-induced neurotoxicity remains unknown. Based on a chronic METH abuse mouse model, we detected the neurotoxicity after METH exposure and determined the intervention effect of ICS and the potential mechanism of action. Here, we found that METH could trigger neurotoxicity, which was characterized by loss of dopaminergic neurons, depletion of dopamine (DA), activation of glial cells, upregulation of α-synuclein (α-syn), abnormal dendritic spine plasticity, and dysfunction of motor coordination and balance. ICS treatment, however, alleviated the above-mentioned neurotoxicity elicited by METH. Our data also indicated that when ICS combated METH-induced neurotoxicity, it was accompanied by partial correction of the abnormal Kelch 2 like ECH2 associated protein 1 (Keap1)-nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and oxidative stress response. In the presence of ML385, an inhibitor of Nrf2, ICS failed to activate the Nrf2-related protein expression and reduce the oxidative stress response. More importantly, ICS could not attenuate METH-induced dopaminergic neurotoxicity and behavioral damage when the Nrf2 was inhibited, suggesting that the neuroprotective effect of ICS on METH-induced neurotoxicity was dependent on activating the Keap1-Nrf2 pathway. Although further research is needed to dig deeper into the actual molecular targets of ICS, it is undeniable that the current results imply the potential value of ICS to reduce the neurotoxicity of METH abusers.

Progressive increase of high-frequency EEG oscillations during meditation is associated with its trait effects on heart rate and proteomics: a study on the Tibetan Buddhist.

Meditation has been a spiritual and healing practice in the East for thousands of years. However, the neurophysiologic mechanisms underlying its traditional form remain unclear. In this study, we recruited a large sample of monks (n = 73) who practice Tibetan Buddhist meditation and compared with meditation-naive local controls (n = 30). Their electroencephalography (EEG) and electrocardiogram signals were simultaneously recorded and blood samples were collected to investigate the integrative effects of Tibetan Buddhist on brain, heart, and proteomics. We found that the EEG activities in monks shifted to a higher frequency from resting to meditation. Meditation starts with decrease of the (pre)frontal delta activity and increase of the (pre)frontal high beta and gamma activity; while at the deep meditative state, the posterior high-frequency activity was also increased, and could be specified as a biomarker for the deep meditation. The state increase of posterior high-frequency EEG activity was significantly correlated with the trait effects on heart rate and nueropilin-1 in monks, with the source of brain-heart correlation mainly locating in the attention and emotion networks. Our study revealed that the effects of Tibetan Buddhist meditation on brain, heart, and proteomics were highly correlated, demonstrating meditation as an integrative body-mind training.

Phenylboronic-acid-based Functional Chemical Materials for Fluorescence Imaging and Tumor Therapy.

Various functional chemical materials have been widely used in imaging and tumor therapy. Targeted ligands such as antibodies, peptides, and small molecules have been combined with functional materials to enhance cellular uptake and are used for active targeting of cancer cells and tumors. Among them, phenylboronic acid (PBA), as a small molecular ligand, has the characteristics of low cytotoxicity and easy modification. PBA improves the cancer cell imaging and tumor treatment effect by binding to glycans on the surface of cancer cells. In this Mini-Review, we introduced the modification strategy and targeting strategy of PBA. We focused on the applications of PBA-based functional materials in fluorescence imaging and tumor therapy. For fluorescence imaging, the potential of PBA-based functional chemical materials in cancer diagnosis and tumor targeting was proved by cell imaging and in vivo imaging. For tumor therapy, we mainly discussed the applications of PBA-based functional chemical materials in chemotherapy, gene therapy, phototherapy, and immunotherapy. PBA-based functional chemical materials provide a useful method for cancer diagnosis and treatment.

Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial.

BACKGROUND: Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVES: We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS: In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS: During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). CONCLUSIONS: There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

Screening influencing factors of blood stasis constitution in traditional Chinese medicine / 数字中医药（英文）

@#Objective To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine (TCM) constitution identification. Methods Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors (gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors (sleep time, age, and mother's age at birth) on the constitution of the two groups were analyzed. In the single-factor analysis, the Pearson's chi-square test was selected for the categorical variable, and the independent sample t test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution; the binary logistic stepwise regression method was selected for the multi-factor analysis. Results The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson's chi-square test yielded significant differences (P < 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples t test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations (P < 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types (P > 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution (P < 0.05). Conclusion Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.